The interaction of the tumor cell with its extracellular matrix may play an important role in determining its metastatic and invasive properties. We have identified, isolated, and characterized cDNA clones of the human and the mouse 37 kDa laminin receptor precursor (37LRP) of the 67 kDa high affinity laminin receptor (67LR). The 67LR is expressed to a greater degree in metastatic tissues than in benign conditions in a variety of tissue-specific neoplasms. The 37LRP contains a laminin binding site that is conserved throughout evolution in organisms that either synthesize or bind to laminin. Prokaryotic and invertebrate homologs of the 37LRP have ribosome binding activity and the human gene was recently renamed RPSA (ribosome protein small subunit A) by the Human Genome Project. It is presumed that vertebrate 37LRP proteins are multifunctional with both laminin- and ribosome-binding properties. The human and chicken RPSA genes were recently cloned and analyzed. Human and chicken genes have the same exon-intron structure. The human gene was localized to chromosome 3p, band 21 and contains 7 exons that span 6 kb. The 5' region that flanks exon 1 does not contain a TATA box but contains other regulatory motifs including five Sp1 sites, a glucocorticoid responsive element, an AP1 site, and a metal responding element. Intron 1 is GC rich and contains seven Sp1 sites, suggesting it may participate in the regulation of RPSA gene expression. Indeed, recent evidence from reporter gene transfection experiments demonstrates negative transcriptional regulatory elements within intron 1. Like many genes that encode ribosome binding proteins, an intron of the human gene was reported to contain the full sequence for a small nucleolar (sno) RNA. We recently discovered that a second intron of the gene encodes a different snoRNA. In addition, we found that the Drosophila ortholog of the RPSA gene contains a snoRNA-like sequence in its only intron. The introduction of RPSA antisense constructs into metastatic cancer cells resulted in a shortened half-life of the sense mRNA and also decreased cell motility and attachment to laminin. These data are consistent with the model that the RPSA is a precursor to a cell surface laminin binding protein, in addition to its function in the ribosome.